Independent effects of interleukin-1 on proteoglycan breakdown, proteoglycan synthesis, and prostaglandin E2 release from cartilage in organ culture.

Exposure of bovine nasal cartilage in culture to interleukin-1 (IL-1) leads to a time- and concentration-dependent stimulation of proteoglycan breakdown and prostaglandin E2 (PGE2) release, and to inhibition of proteoglycan synthesis. The threshold levels of IL-1 required for initiating these effects were different, and IL-1 was 10 times more potent in inhibiting synthesis than in stimulating breakdown of proteoglycan. Kinetic studies indicated that the effects on proteoglycan metabolism occurred earlier (16-24 hours) than those for PGE2 release (48 hours). Selective effects were observed with inhibitors. Nonsteroidal antiinflammatory drugs blocked PGE2 production in response to IL-1, but had no effect on proteoglycan metabolism, and the antiarthritic drugs that blocked IL-1-stimulated breakdown augmented the inhibition of proteoglycan synthesis. We suggest that the effects of IL-1 on proteoglycan breakdown, proteoglycan synthesis, and PGE2 release are mediated by independent post-receptor mechanisms.